In this review article, by well-known tissue engineer Donald Ingber, he discusses the various factors that influence cellular growth and development. Ingber notes that mechanical forces, such as tension and compression, can have a significant impact on cell division, growth, and communication, particularly in the lungs during inhalation and exhalation. Utilizing 3D cell cultures and lung-on-a-chip technology could potentially replicate these mechanical forces, leading to more accurate representation of human biology in drug testing. This could eventually lead to animal studies becoming obsolete!

The following research papers discuss the potential of microfluidic devices and surface patterning to create advanced cell culture models. For example, Khademhosseini et al. discuss the potential for microfluidic devices to assess the problems with modern 3D tissue models. For example, Langer et al. discuss how standard cell cultures cannot replicate the repetitive mechanical strain that human organs such as lungs and gut undergo every day. The authors also discuss how oxygen and protein transport through these tissue scaffolds does not accurately mimic human conditions. While attempts have been made to improve cell-cell connectivity and nutrient transport in 3D cultures, microfluidic technology provides a potential pathway to generate accurate and viable organ models.

Pampaloni et al. claim that 3D cell culture models help mimic the functions of living tissues to predict the cellular responses of real organisms.

The authors believe that 3D cell cultures will have a strong impact on drug screening and can also decrease the use of laboratory animals for drug discovery and development.

Zhang et. al have developed a multi-channel 3D microfluidic cell culture system with compartmentalized microenvironments to culture different 3D cells that can simultaneously represent different organs in the body! This system demonstrates potential applications in human drug screening to supplement or replace animal models.

Nel et. al discusses potential toxic effects of nanomaterials; structures with one dimension of 100 nanometers or less, that are used in a variety of commercial applications such as semiconductors, drug carriers, and cosmetics. Due to their size, nanoparticles exhibit unique properties, but this also makes them potentially harmful to biological systems and the environment. The authors caution that it is crucial to establish principles and testing protocols to ensure the safe manufacture and use of nanomaterials in the market.

Takayama et. al report a new way of manufacturing microchannels out of PDMS that can be smaller than the width of a human hair! The process involves the controlled etching of a PDMS slab to create novel microchannel geometries. The authors have high hopes for their technology: "We believe that these procedures will enable new types of studies in fundamental cell biology, and that they will also be useful in the microfabrication of devices that require a high-level of control over the behavior of cells"

Mahler et. al have developed a microscale cell culture of the GI tract that includes digestion, a mucus layer, and cell populations. This can provide rapid, inexpensive, and accurate predictions of the body's response to drugs and chemicals, as demonstrated by their experiments with acetaminophen!

Huh et. al have developed a microfabricated airway system that can mimic physiologic or pathologic liquid flows found in the respiratory system! The authors engineered an on-chip human airway and demonstrated cellular-level lung injury, similar to symptoms characteristic of a wide range of pulmonary diseases.

Davilla et. al. discuss the advantages and disadvantages of lab-grown cell cultures that can mimic the function of kidneys and livers. While these cultures are inexpensive and can help measure drug-specific tissue interactions at a cellular/molecular level, the models do not accurately account for molecular transport and toxicity interactions between tissues and organs. This is because the cultures are grown on a flat surface, rather than in a 3D organ-like configuration. The authors conclude that cell culture models are a step towards pharmaceutical testing that does not use animal models, but further development is needed to effectively mimic the human body's reactions to various drugs.

The movement of something (nanoparticles) from one place (alveolar) to another (capillary).

A "germ", bacterium, virus, or other microorganism that can cause disease.

This landmark paper led to the creation of Emulate, a biotechnology company focused on commercializing "organ-on-a-chip" systems across multiple organs and applications. It has been shown that Emulate human Liver-Chips can predict drug-induced liver injury better than animal models.

Read more at Emulate: https://emulatebio.com/about/

In 2022, the US lifted the federal mandate (since 1938) that required experimental drug testing on animals prior to human clinical trials. Therefore, microsystems, like "organ-on-a-chip", can be used as an alternative to animal testing.

Read more at Wired: https://www.wired.com/story/the-us-just-greenlit-high-tech-alternatives-to-animal-testing/

Many researchers believe that "organ-on-a-chip" microdevices are the future of drug testing and physiological modeling, potentially replacing animal models.

Read more at: https://data.europa.eu/doi/10.2760/725821